This is a Phase 1, two part, study of patients with recurrent Head and Neck Cancer (HNC), who in the opinion of their physician, cannot be satisfactorily treated with surgery, radiation or platinum chemotherapy. Part I is a drug dose-escalation, fixed low fluency light application study to determine the drug dose that can be safely given to saturate the epidermal growth factor receptor (EGFR) at the tumor.

Part II is a light dose-escalation, fixed drug dosing infusion study to determine the optimal light application, in combination with the Part I drug dose, needed to achieve clinical response with an acceptable safety profile. Interim analysis will be performed after completion of Part I and prior to initiation of Part II.

Photoimmunotherapy (PIT) is a new cancer targeted technology invented at the National Cancer Institute, USA. PIT utilizes monoclonal antibodies conjugated to a dye (abbreviated as IR700) that can be activated upon near-infrared light illumination to induce rapid cell killing only at cells expressing the antigen and only after antibody binding to the cellular antigen. The requirement of light-induced activation and antigen-antibody binding to induce cell killing enables the selective destruction of only cancer cells with minimum damage of healthy tissue surrounding the tumor cells. Photoimmunotherapy requires two treatment steps: (i) the administration of the drug by infusion AND (ii) the irradiation of the tumor with 690 nm light using sufficient energy (light fluence) to induce cell killing. Light irradiation is typically applied between 24 hours to 72 hours post drug administration to enable drug distribution within the tumor.

The experimental drug therapy, RM-1929, is an injectable formulation consisting of a chemical conjugate of the dye IR700 with the FDA approved antibody, Erbitux® (Cetuximab), that targets EGFR antigens. EGFR is highly expressed in squamous cell carcinomas of the head and neck, and Erbitux® Photoimmunotherapy with RM-1929 may result in significant improvements of is clinically used to treat HNC and colorectal cancers. It is expected that systemic administration of RM-1929 will lead to tumor accumulation of RM-1929 and binding to EGFR expressed at cancer cells. After RM-1929 administration, subsequent light irradiation should induce rapid tumor destruction of recurrent HNCs and provide an effective therapy to manage the disease. Preclinical pharmacology demonstrated that light-induced activation of RM-1929 elicits rapid tumor destruction of human cancer xenografts implanted in mice progression free survival and overall survival with better quality of life than when using existing standard of care (SOC) approaches.

Part I of this study will determine the safety and pharmacokinetics of RM-1929 administered by IV infusion using a single low energy localized light irradiation. Part II of this study will optimize the treatment by evaluating safety and clinical response using a fixed dose level of RM-1929 - determined from Part I of this study - and performing a light escalation study using increasing irradiation fluences at the tumor to optimize anticancer Photoimmunotherapy.

Inclusion Criteria:

• Patients with recurrent squamous carcinoma of the Head and Neck, who in the opinion of their treating physician, cannot be satisfactorily treated with surgery, radiation or platinum chemotherapy. Diagnosis must be confirmed by biopsy and histopathology.
• Patient must have received prior systemic platinum-based chemotherapy for treatment of their head and neck cancer, unless in the opinion of the medical oncologist, the use of platinum-based chemotherapy is contraindicated or not recommended, e.g., renal impairment, allergy to platinum compounds, age, liver disease, myelosuppression, neuropathy, hearing loss, etc.
• Patients must have life expectancy > 6 months based on investigator judgment.
• Male or female patients at least 18 years old. Female patients must not be pregnant or breast feeding and must be practicing a medically acceptable form of birth control, be sterile or post-menopausal. Females of childbearing potential (FCBP) is defined as premenopausal women capable of becoming pregnant. This includes women who are post-menopausal for at least 12 months after the last menses. FCBP must agree to use a medically acceptable form of birth control during the study and for at least 6 months after discontinuation of Erbitux® or study medication. Females must agree not to breast feed during the study and for at least two months after discontinuation of Erbitux® or study medication. Male patients should be using a double barrier protection method that is a medically acceptable form of birth control during the study or be sterile.
• Patients must have an ECOG score of 0 - 2.
• Patient or legal representative must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure.

Exclusion Criteria:

• Patients with a history of or who display significant infusion reactions (Grade 3 or greater) during the pre-treatment with a 100 mg dose of Erbitux®
• Patients on chemotherapy or Erbitux® therapy or radiation therapy within 4 weeks of enrollment, except for treatment as part of this protocol.
• Tumor invading a major blood vessel (such as the carotid artery).
• Tumor is not clearly shown on a CT scan or clinically measurable.
• Location and extension of the tumor precludes an effective PIT.
• Patients with impaired hepatic function (alkaline phosphatase (hepatic; ALP), aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 3 times the upper normal limits, or total serum bilirubin > 2 mg/dL.
• Patients with impairment of renal function (serum creatinine > 2 mg/dL).
• Unwilling or unable to follow protocol requirements.
• Any condition which in the Investigator's opinion deems the patient an unsuitable candidate to receive study drug.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Patient requires examinations or treatments within 4 weeks after study drug administration where they would be exposed to significant light, e.g., eye examinations, surgical procedures, endoscopy, etc.